Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.

The moderating effect of resting heart rate variability on the relationship between internet addiction tendency and brain morphology.

Previous neuroimaging studies have investigated brain morphology associated with internet addiction tendency (IAT) in healthy subjects. However, whether resting vagally-mediated heart rate variability (HRV) exerting influences on the association of IAT and brain morphology remains unclear. This study used voxel-based morphometry (VBM) and multiple regression analyses to assess the interaction effect of IAT and resting vagally-mediated HRV on regional grey matter volumes in 82 healthy subjects. To further illustrate the observed interaction effect, the moderated hierarchical regression analysis was performed. The results showed that resting vagally-mediated HRV moderated the relationship between IAT scores and grey matter volume (GMV) in the precuneus and cerebellum. Specifically, individuals with higher resting vagally-mediated HRV showed a significant positive relationship between IAT scores and GMV in the precuneus, whereas individuals with lower resting vagally-mediated HRV showed a significant negative relationship between IAT scores and GMV in the precuneus. In addition, IAT scores were negatively correlated with GMV in the cerebellum among individuals with lower resting vagally-mediated HRV, but not among individuals with higher resting vagally-mediated HRV. These findings have demonstrated a moderating role of resting vagally-mediated HRV on the association of IAT and brain morphology.

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar epithelial cell injury and lung fibroblast overactivation. At present, only two drugs are approved by the FDA for the treatment of IPF, including the synthetic pyridinone drug, pirfenidone, and the tyrosine kinase inhibitor, nintedanib. Avitinib (AVB) is a novel oral and potent third-generation tyrosine kinase inhibitor for treating non-small cell lung cancer (NSCLC). However, the role of avitinib in pulmonary fibrosis has not yet been established. In the present study, we used in vivo and in vitro models to evaluate the role of avitinib in pulmonary fibrosis. In vivo experiments first verified that avitinib significantly alleviated bleomycin-induced pulmonary fibrosis in mice. Further in vitro molecular studies indicated that avitinib inhibited myofibroblast activation, migration and extracellular matrix (ECM) production in NIH-3T3 cells, mainly by inhibiting the TGF-ß1/Smad3 signalling pathways. The cellular experiments also indicated that avitinib improved alveolar epithelial cell injury in A549 cells. In conclusion, the present findings demonstrated that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation.

Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: a systematic review and meta-analysis.

BACKGROUND: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. METHODS: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. RESULTS: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. CONCLUSION: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.

Increased 90-Day Mortality in Spontaneously Breathing Patients With Paraquat Poisoning: In Addition to Disease Severity, Lung Strain May Play a Role.

OBJECTIVES: 1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. DESIGN: Prospective study. SETTING: A university hospital ICU. PATIENTS: One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. INTERVENTIONS: A standardized treatment protocol. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021-3.296; p < 0.001) was most strongly associated with mortality, such that neither blood paraquat concentration nor PaO2 provided any additional prognostic information. The ratio of residual volume to total lung capacity as a percentage of the predicted value (adjusted hazard ratio, 1.041; 95% CI, 1.026-1.057; p < 0.001) was the only variable that added prognostic value to Exp(%Wpoor/15). While controlling for Exp(%Wpoor/15) and percentage of predicted residual volume/total lung capacity, increases in dynamic strain (adjusted hazard ratio, 2.041/0.1 U; 95% CI, 1.283-3.248; p = 0.003) and/or decreases in respiratory system reactance at 5 Hz (adjusted hazard ratio, 1.19/0.1 U; 95% CI, 1.03-1.386; p = 0.02) were independently associated with increased 90-day mortality. CONCLUSIONS: In patients with paraquat poisoning, Exp(%Wpoor/15) and percentage of residual volume/total lung capacity are independent prognostic indicators. Higher dynamic strain and increased ventilation heterogeneity during unassisted spontaneous breathing were associated with worsened survival independent of Exp(%Wpoor/15) and percentage of residual volume/total lung capacity.

A multicenter RCT of noninvasive ventilation in pneumonia-induced early mild acute respiratory distress syndrome.

RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.

Grey Matter Volumes in the Executive Attention System Predict Individual Differences in Effortful Control in Young Adults.

Effortful control (EC), considered as one component of temperament, describes an individual's capacity for self-regulation. Previous neuroimaging studies have provided convergent evidence that individual differences in EC are determined by the functioning of neural systems subserving executive attention, primarily comprising the anterior cingulate cortex (ACC) and the lateral prefrontal cortex (PFC). Notwithstanding, as previous neuroimaging findings highlighted the structural neural bases of EC in adolescence, during which the PFC is prominently remodeled, the underlying neuroanatomical substrates of EC remain uncertain in young adults. In this study, we included 246 healthy young adults and used voxel-based morphometry analysis to investigate the relationship between EC and grey matter (GM) volumes. Additionally, permutation testing and cross-validation were applied to determine whether GM volumes in the detected regions could predict individual differences in EC. Our results revealed that EC was associated with GM volumes in the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA), demonstrating that these two regions may play a crucial role in EC. Furthermore, the identified regional GM volumes reliably contribute to the prediction of EC confirmed by cross-validation. Overall, these findings provide further evidence for the involvement of the executive attention system in EC, and shed more light on the neuroanatomical substrates of EC in young adulthood.

Pulse Pressure Variation Adjusted by Respiratory Changes in Pleural Pressure, Rather Than by Tidal Volume, Reliably Predicts Fluid Responsiveness in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: 1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. DESIGN: Prospective study. SETTING: Forty-bed university hospital general ICU. PATIENTS: Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. INTERVENTIONS: Fluid challenge, 500 mL saline over 20 minutes. MEASUREMENTS AND MAIN RESULTS: Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88-0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88-0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69-0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94-2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05-2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36-3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84-0.99) compared with 0.76 (95% CI, 0.61-0.87) otherwise (p = 0.02). CONCLUSIONS: In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume.

Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB, 100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-ß1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

Distinct patterns of spontaneous brain activity between children and adults with anisometropic amblyopia: a resting-state fMRI study.

PURPOSE: To detect the altered spontaneous brain activity patterns in children and adults with anisometropic amblyopia using resting-state functional magnetic resonance imaging (rs-fMRI) technique combined with the amplitude of low-frequency fluctuation (ALFF) method. METHODS: Thirty-two monocular anisometropic amblyopia and 34 normal-sight controls were divided into child group and adult group. Rs-fMRI was performed in all participants and analysis of ALFF value within the whole brain was conducted in each subject. ALFF value differences between the patients and controls in the two groups were compared via an independent two-sample t test. RESULTS: The amblyopic children mainly exhibited increased ALFF in part of the bilateral calcarine (BA17), the left middle occipital gyrus (BA18/19), and the left postcentral gyrus (BA2). By contrast, the amblyopic adults showed decreased ALFF in the bilateral precuneus cortex (part of BA7), and the standardized ALFF value of bilateral precuneus were correlated with the amount of anisometropia of the amblyopic adults. CONCLUSIONS: Rs-fMRI is an effective noninvasive technique for exploring brain activity of the anisometropic amblyopia. Our findings demonstrated that brain activity changed both in amblyopic children and adults under the resting state, and revealed the differences in spontaneous activity patterns between the amblyopic children and adults.

Dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in a mouse model of experimental silicosis.

CONTEXT: Silicosis is a devastating, irreversible lung fibrosis condition exposed to crystalline silica. The mononuclear phagocyte system plays an important role in the pathogenesis of silicosis. OBJECTIVE: The present study was aimed to explore the dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in experimental silicosis model. MATERIALS AND METHODS: A mouse model of lung fibrosis was developed with crystalline silica particles (2 mg/40 µL via oropharyngeal instillation) using male C57BL/6 mice, and were killed on days 1, 3, 7, 14, and 28. The lung inflammation and fibrosis was investigated using hematoxylin-eosin staining and bronchoalveolar lavage fluid (BALF) analysis, Masson's trichrome staining, and immunofluorescence. Circulating monocyte subsets (Ly6C(hi) and Ly6C(lo)), polarization state of BALF-derived alveolar macrophages (AMϕ) and lung interstitial macrophages (IMϕ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. RESULTS: The percentage of Ly6C(hi) monocytes significantly increased on day 1 after silica exposure, which reached the peak level from day 7 till day 28. Moreover, M2 (alternative activation) AMϕ (PI - CD64 + CD206+) was dramatically and progressively increased from day 1 to day 28. A parallel increase in IMϕ with M2 polarization (PI-CD64 + CD11b + CD206+) was also observed from day 1 to day 28. CONCLUSION: Our data demonstrate a dynamic view of mononuclear phagocyte change in three compartments after silica challenge, which highlights the remodeling of mononuclear phagocyte system as a potential therapeutic target for silicosis.

Continuous plasma perfusion of dual cartridges in series: rationale and early clinical experience.

To improve the efficiency of plasma perfusion on eliminating plasma paraquat (PQ), we designed continuous plasma perfusion of dual cartridges in series (CPPDCS) on Diapact Braun CRRT machine. The goals of this study were to evaluate the effective of CPPDCS on paraquat removal in patients with acute paraquat intoxication. Our results show that the PQ clearance rate of dual cartridges was significantly higher than that of single cartridge at 1st, 2nd, 3rd, and 4th plasma perfusion. Compared with single-cartridge plasma perfusion, CPPDCS significantly reduced the frequency of cartridge replacement, shorten the time of perfusion. These results indicate that CPPDCS is effective than plasma perfusion of single cartridge on PQ clearance rate and may provide an effective treatment for PQ poisoning.

[A comparison study of diagnostic value between the old and revised guidelines in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To compare the strengths and limitations of the old and revised guidelines for the diagnosis in patients with idiopathic pulmonary fibrosis(IPF). METHODS: Patients who were admitted and diagnosed as interstitial lung diseases (ILDs) in our hospital from 2009 to 2014 were enrolled in our study.Eachpatient was reevaluated respectively according to the old and revised guidelines of IPF. RESULTS: A total of 553 cases were initially reviewed, among whom 355 cases were excluded for pulmonary fibrosis secondary to definite underlying diseases, 28 excluded due to high resolution computed tomography(HRCT) not done, 26 excluded because serum immunology examination was not available.The remaining 144 cases were finally enrolled in this study including 92 males and 52 females with median age 21-92 (68 ± 11) years old. Twenty five patients (17.4%, 25/144) met the diagnostic criteria of IPF by the old guideline.While by the revised guideline, 53 patients (36.8%, 53/144) were diagnosed as classical IPF, 29 patients(20.1%, 29/144) as probable cases, another 69 non-IPF patients accounting for 43.1% (62/144). The result revealed that there's a significant difference between the two guidelines in the diagnosis of IPF. CONCLUSIONS: The revised guideline favors an early diagnosis of IPF and simplifies the diagnostic process.However the possibility of over diagnosis or missed diagnosis by the revised guideline does exist.On the other hand, despite of the delayed diagnosis by the old guideline, it may reduce the misdiagnosis of IPF in some circumstance.

Clinical management of organophosphate poisoning in pregnancy.

BACKGROUND: Acute organophosphorus pesticide poisoning during pregnancy may lead to spontaneous abortion. Now, there is no definite strategy focused on maintaining pregnancy. METHOD: This is a retrospective analysis of 2 cases of organophosphorus poisoning during pregnancy. All patients received penehyclidine hydrochloride injection,until the tracheobronchial tree is cleared of the secretions, and most secretions were dried. In addition, magnesium sulfate was used in one woman for the correction of hyperdynamic uterine activity. RESULTS: Two women all survived, one fetus died of spontaneous abortion, and one fetus died of incoordinate uterine action. The 2 women had no significant complications during postpartum period. CONCLUSION: Penehyclidine hydrochloride and magnesium sulfate may be used to treat organophosphorus during pregnancy. However, futher study and new experimental need to be designed.

[Outbreak of six cases of nosocomial Legionella pneumophila pneumonia].

OBJECTIVES: To describe the clinical characteristics, diagnosis, treatment and the causes of outbreak of nosocomial pneumonia due to Legionella pneumophila. METHODS: The medical records of 6 cases of nosocomial Legionella pneumophila pneumonia were retrospectively reviewed, and the clinical data of clinical presentation, treatment, and etiologic diagnosis were analyzed. RESULTS: The 6 patients were health care providers of the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Logistics University of PAPF. There were 5 female and 1 male patients, aged 23 to 27 years. The diagnosis of Legionella pneumonia was made based on a positive Legionella urinary I antigen test. In all the 6 cases, the disease was attributable to inhaling contaminated aerosols produced by the air conditioning system in our hospital. All the 6 patients presented with fever of 37.5-39 °C, and productive cough. One patient had anorexia, dyspnoea, and pleuritic chest pain, while headache was reported in 3 patients. Physical examinations revealed lung rales in 3 patients. Single or multiple patchy infiltrates were found on Chest CT in all patients. However, the typical extrapulmonary manifestations of Legionnaires' disease, including relative bradycardia, hyponatremia, hypophosphatemia and diarrhea, were not present in the 6 patients. Neither neurological abnormalities nor renal involvement were observed. CONCLUSIONS: Our data demonstrated that Legionella pneumonia may be mild with atypical laboratory findings and clinical manifestations, with fever, cough, chest tightness, headache, etc. The radiologic manifestations of Legionella pneumonia were single or multiple patchy infiltrates, similar to those of viral pneumonia, and therefore their differential diagnosis was needed. Legionella pneumophila can outbreak through the respiratory tract, in public places with central air-conditioning system, hot water piping systems and hospitals, and therefore microbiological monitoring, cleaning and disinfection of the water system was required for prevention of the outbreaks of Legionnaires' disease.

[Analysis of prognostic value of initial serum paraquat concentration in patients with paraquat poisoning].

OBJECTIVE: To investigate the prognostic values of initial serum paraquat (PQ) concentration and time lag after PQ ingestion in patients with PQ poisoning. METHODS: A retrospective analysis was performed on 189 patients who ingested PQ between 2.5 and 48 h before admission. The values of initial serum PQ concentration and time lag after PQ ingestion for the prognosis after poisoning were analyzed by the receiver operating characteristic (ROC) curve and multiple logistic regression analysis. RESULTS: The serum PQ concentration of non-survivors was significantly higher than that of survivors (P<0.01) , and the time lag after PQ ingestion of non-survivors was significantly longer than that of survivors (P<0.01). The ROC curve analysis showed that the area under the ROC curve (AUC) showed no significant difference between initial serum PQ concentration and serum PQ concentration-time data when the time lag after PQ ingestion was between 2.5 and 48 h (z=0.563, P=0.574) ; the AUC showed a significant difference between initial serum PQ concentration and serum PQ concentration-time data when the time lag after PQ ingestion was between 2.5 and 6 h (z=2.199, P=0.034) and between 6 and 48 h (z=2.525, P=0.012). CONCLUSION: Initial serum PQ concentration has a better predictive power than serum PQ concentration-time data in evaluating the prognosis of patients when the time lag after PQ ingestion is within 6 h. However, serum PQ concentration-time data has a better predictive power than PQ concentration alone in evaluating the prognosis of patients when the time lag after PQ ingestion is between 6 and 48 h.

Specific frequency bands of amplitude low-frequency oscillation encodes personality.

The biological model of extraversion and neuroticism identified by Eysenck has stimulated increasing interest in uncovering neurobiological substrate of the two fundamental dimensions. Here we aim to explore brain disturbances underlying extraversion and neuroticism in 87 healthy individuals using fractional amplitude of low-frequency fluctuations (LFF) on resting-state functional magnetic resonance imaging. Two different frequency bands, Slow-5 (0.01-0.027 Hz) exhibiting higher power and involving larger brain regions, and Slow-4 (0.027-0.073 Hz) exhibiting less power and emerging locally, were analyzed. Our results showed a positive correlation between LFF amplitude at Slow-5 and extraversion in medial prefrontal cortex and precuneus, important portions of the default mode network, thus suggesting a link between default network activity and personality traits. LFF amplitude at Slow-5 was correlated positively with neuroticism in right posterior portion of the frontal lobe, further validating neuroticism with frontal lateralization. In addition, LFF amplitude at Slow-4 was negatively associated with extraversion and neuroticism in left hippocampus (HIP) and bilateral superior temporal cortex (STC) respectively, supporting the hypothesized (inverse) relationship between extraversion and resting arousal, also implying neural circuit underlying emotional process influencing on personality. Overall, these findings suggest the important relationships, between personality and LFF amplitude dynamic, depend on specific frequency bands.

Analysis of cerebrospinal fluid flow dynamics and morphology in Chiari I malformation with cine phase-contrast magnetic resonance imaging.

BACKGROUND: To determine cerebrospinal fluid (CSF) dynamics and morphology in Chiari I malformation (CMI) and assess the response to surgery of the posterior cranial fossa, we examined midsagittal imaging along with anterior cervical 2-3 (AC2-3), posterior cervical 2-3 (PC2-3), and aqueduct CSF flow hydrodynamics in axial imaging by using cine phase-contrast magnetic resonance imaging (PCMR). METHOD: We examined 52 patients with CMI, both with and without syringomyelia (SM), pre-/post-surgery, and compared them to 17 healthy volunteers. Statistical analyses included paired t-tests, independent-samples t-tests, binary logistic regression, and crosstab with MedCalc software. RESULTS: Patients with CMI had significantly shorter clivus length and larger tentorial angle than the healthy controls (P = 0.004, P = 0.019, respectively). The AC2-3 cranial/caudal peak velocity (PV), PC2-3 cranial/caudal PV and aqueduct cranial peak PV of patients with CMI were significantly lower than healthy volunteers pre-surgery (P = 0.034 AC2-3 cranial PV, P = 0.000002 AC2-3 caudal PV; P = 0.046 PC2-3 cranial PV, P = 0.015 PC2-3 caudal PV; P = 0.022 aqueduct cranial PV) and increased after surgery (P = 0.024 AC2-3 cranial PV, P = 0.002 AC2-3 caudal PV; P = 0.001 PC2-3 cranial PV, P = 0.032 PC2-3 caudal PV; P = 0.003 aqueduct cranial PV). The aqueduct caudal PV of patients with CMI was higher than that of healthy controls (P = 0.004) and decreased post-surgery (P = 0.012). Patients with pre-surgery PC2-3 cranial PV >2.63 cm/s and aqueduct cranial PV >2.13 cm/s, respectively, experienced primary symptom improvement after surgery. CONCLUSIONS: The innate bony dysontogenesis in patients with CMI contributes to tonsilar ectopia and exacerbates CSF flow obstruction. A pressure gradient that existed between SM and SAS supports the perivascular space theory that is used to explain SM formation. Our findings demonstrate that PCMR maybe a useful tool for predicting patient prognosis.

[The correlation of helper T lymphocyte 1/helper T lymphocyte 2 with clinical and image features in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To identify whether the helper T lymphocyte 1 (Th1)/helper T lymphocyte 2 (Th2) of patients' serum and bronchoalveolar lavage fluid (BALF) at admission could represent the severity of idiopathic pulmonary fibrosis (IPF) and whether its change at six months could predict the progression of the disease. METHODS: Eighty-three patients with IPF were subjected to pulmonary function tests (PFTs), dyspnea scores, arterial blood gas analysis, six-minute walk test (6MWT) and high-resolution computed tomography (HRCT). The serum and BALF specimen of these patients were obtained as well as 20 control serum and 10 control BALF specimen. A total of 55 patients were followed up, and their BALF and serum levels of interferon γ(IFNγ) and IL-4 were detected by enzyme-linked immunoadsorbent assay (ELISA). The correlation between the IFNγ/IL-4 levels (at admission and the change of that at six months follow-up) and the clinical, physiological and image features in the IPF patients were analyzed. RESULTS: The baseline serum and BALF level of IFNγ/IL-4 (0.8 ± 0.3) in the IPF patients was lower than that in the control group (1.4 ± 0.2), which showed significant correlation with the course of disease, dyspnea scores, FEV1%, FVC%, TLC%, maximum desaturation, 6MWD and CT-fib (all P values<0.05). The serum level of IFNγ/IL-4 showed positive correlation with CT-alv (r = 0.340, P<0.01). During follow-up, no statistic difference was found in the serum levels of IFNγ, IL-4 and IFNγ/IL-4 between the IPF patients with or without glucocorticoids treatment. There were significant aggravation in the dyspnea scores, FEV1%, FVC%, CT-alv, CT-fib, IFNγ and IL-4 at six months follow-up. Significant correlation had been showed between the change of the serum IFNγ/IL-4 level with the changes of the dyspnea scores, FVC%, TLC%, DLCO%, 6MWD and CT-fib in the IPF patients (P < 0.05). CONCLUSIONS: There are disequilibrium of the Th1/Th2 in the serum and the BALF of the IPF patients. The Th1/Th2 level could represent severity of the disease, and the serum level change of Th1/Th2 in the follow-up could predict the progression of the diseases in the IPF patients.

Diagnosis of mycobacterium avium complex infection utilizing metagenomics next-generation sequencing: a case report.

Mycobacterium avium-intracellulare complex (MAC) is a type of nontuberculous mycobacteria (NTM) and is associated with underlying pulmonary diseases, such as chronic obstructive pulmonary disease, bronchiectasis, chronic aspiration or recurrent pneumonia, inactive or active tuberculosis, pneumoconiosis, and bronchogenic carcinoma. The risk factors for NTM-PD include host, drug, and environmental factors. In this report, we present the case of a 61-year-old man who developed bilateral lung nodules and was experiencing severe hemoptysis. The repeat acid-fast bacilli test performed on both sputum and bronchoalveolar lavage fluid (BALF) samples showed a negative result, as did the GeneXpert test. We employed metagenomic next-generation sequencing (mNGS) to analyze the lung nodule and BALF samples collected from the patient. Both samples tested positive for MAC within 3 days. In addition, traditional MAC culture, conducted for 2 months, confirmed the growth of MAC in the patient's BALF. Then, the patient was treated accordingly. Following treatment, a high-resolution chest computed tomography scan revealed a significant reduction in lung nodules of the patient after 2 months. These results indicate that MAC-associated lung nodules were responsible for the patient's symptoms, emphasizing the need for vigilance in diagnosing MAC infection in the patient without predisposing conditions. Furthermore, these results highlight the potential utility of mNGS as a promising rapid diagnostic tool for MAC infection and its potential role in the diagnosis of NTM disease.